1. Field of the Invention
The present invention relates to diagnosis of spinal muscular atrophy, and in particular relates to a method for diagnosing spinal muscular atrophy by capillary electrophoresis.
2. Description of the Related Art
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of motor neurons in the anterior horn of a spinal cord, leading to muscular paralysis and atrophy. SMA is traditionally categorized into three types, according to the age and severity. For children with SMA, SMA is categorized as: type I, severe; type II, intermediate; and type III, mild. For adults with mild symptoms of SMA, SMA is categorized as type IV. Additionally, for prenatal onset of very severe symptoms of SMA and early neonatal death due to SMA, SMA is categorized as type 0 (Eur J Paediatr Neurol 1999; 3:49-51; Lancet 1995; 346:1162; Neuromuscul Disord 1992; 2:423-428). SMA occurs in approximately 1 in 6000-10000 live births and has a carrier frequency of 1 in 50. It is the second most common autosomal recessive inherited disorder in humans and the most common genetic cause of infant mortality (Semin Neurol 1998; 18:19-26).
SMA is caused by the homozygous deletion or mutations of the survival motor neuron gene (SMN) including telomeric SMN (SMN1) and centromeric SMN (SMN2) genes. The genes possess two differences, which are substitution of single nucleotides in exon 7 (c 840 C>T) and 8 (G>A) in the cDNAs. Deletion of the SMN1 gene has been reported in approximately 94% of clinically typical SMA-affected patients, and the SMN2 copy number has been found to be related to the disease severity and life length. To diagnose SMA, most techniques quantify the nucleotide difference in exon 7 of SMN1/SMN2. However, it has been found that the SMA in approximate 6% of affected patients, is caused by point mutations at other exons in which SMN1 is present. Therefore, only detection of the difference of SMN1/SMN2 genes in exon 7 could not accurately diagnose the SMA disease in a clinical environment.
Thus, to improve the diagnostic accuracy of the SMA disease in a clinical environment, a novel diagnostics method and diagnosis kit is required.